Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0729233 (Thoracic)
 6,478 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was performed to determine if direct arterial dilating actions of propofol contribute to the drug's hypotensive actions. The effects of propofol were compared with those of thiopental on isolated vascular ring preparations from rat thoracic aorta and pulmonary artery. Thoracic aortic ring responses were evaluated in the presence and absence of endothelium, indomethacin, and N omega-nitro-L-arginine methyl ester (LNAME; a specific inhibitor of endothelium-derived relaxing factor-nitric oxide [EDRF/NO] synthase). Pulmonary artery responses were investigated with intact endothelium. After the induction of active isometric force by a predetermined EC50 dose of phenylephrine for each ring, effects of propofol (30, 100, 300 microM) and thiopental (10, 30, 100 microM) were examined. Propofol caused significant vasodilation in endothelium-intact, endothelium-denuded, and LNAME-treated aortic rings. In the endothelium-intact aortic and pulmonary artery rings, the initial vasodilation due to 30 and 100 microM propofol showed gradual and partial recovery over 15 min; 300 microM propofol caused sustained vasodilation. Endothelium-denuded rings and LNAME-pretreated endothelium-intact rings showed constant and sustained vasodilation with all propofol concentrations. Propofol also caused marked vasodilation in pulmonary arteries. In contrast, thiopental had no vasodilating effect in aortic or pulmonary artery preparations. In control experiments, propofol vehicle (Intralipid) also had no effect on vascular rings. Indomethacin pretreatment induced a dose-dependent vasoconstriction by thiopental in endothelium-intact rings and decreased the vasodilation due to propofol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of propofol and thiopental in isolated rat aorta and pulmonary artery. 851 16

Pregnancy is associated with decreases of blood pressure and vascular sensitivity to vasopressor agents. We have hypothesized that the increased liberation of endogenous vasodilator(s) by the vascular endothelium or other structures could mediate these blunted responses. Thoracic aorta rings of nonpregnant, 21 days pregnant, and first day post partum rats respond similarly to acetylcholine, an endothelium-dependent vasorelaxant. In contrast, the potency of the response to sodium nitroprusside, an endothelium-independent vasorelaxant, is unchanged in tissues of pregnant rats and increased (p less than 0.05) in those of post partum animals. In the presence of indomethacin (10 mumol/L) the three groups of tissues show a decreased potency. The effects of phenylephrine on aortic rings of both nonpregnant and pregnant rats are markedly increased in the presence of Ng-monomethyl-L-arginine. Indeed, the concentration producing 50% of the maximum response of phenylephrine decreases (p less than 0.001) from 50.7 to 8.02, from 93.8 to 37.6, and from 60.4 to 5.97 nmol/L with the use of Ng-monomethyl-L-arginine (0.1 mmol/L) in rings from nonpregnant, pregnant, and postpartum rats, respectively. Simultaneously, the maximum response to phenylephrine increases markedly in the three groups of tissues. In the presence of Ng-monomethyl-L-arginine, indomethacin does not influence the response to phenylephrine. Our results do not support the possible involvement of an endogenous vasodilator (prostaglandin-like or endothelium-derived) in the blunted responses to vasoconstrictors during pregnancy.
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PMID:Prostaglandin- or endothelium-mediated vasodilation is not involved in the blunted responses of blood vessels to vasoconstrictors in pregnant rats. 153 53

1. We have investigated the effects of aminoguanidine, a relatively selective inhibitor of the cytokine-inducible isoform of nitric oxide synthase (iNOS), on the delayed circulatory failure, vascular hyporeactivity to vasoconstrictor agents, and iNOS activity in a rat model of circulatory shock induced by bacterial endotoxin (E. coli lipopolysaccharide; LPS). In addition, we have evaluated the effect of aminoguanidine on the 24 h survival rate in a murine model of endotoxaemia. 2. Male Wistar rats were anaesthetized and instrumented for the measurement of mean arterial blood pressure (MAP) and heart rate (HR). Injection of LPS (10 mg kg-1, i.v.) resulted in a fall in MAP from 115 +/- 4 mmHg (time 0, control) to 79 +/- 9 mmHg at 180 min (P < 0.05, n = 10). The pressor effect of noradrenaline (NA, 1 microgram kg-1, i.v.) was also significantly reduced at 60, 120 and 180 min after LPS injection. In contrast, animals pretreated with aminoguanidine (15 mg kg-1, i.v., 20 min prior to LPS injection) maintained a significantly higher MAP (at 180 min, 102 +/- 3 mmHg, n = 10, P < 0.05) when compared to rats given only LPS (LPS-rats). Cumulative administration of aminoguanidine (15 mg kg-1 and 45 mg kg-1) given 180 min after LPS caused a dose-related increase in MAP and reversed the hypotension. Aminoguanidine also significantly alleviated the reduction of the pressor response to NA: indeed, at 180 min, the pressor response returned to normal in aminoguanidine pretreated LPS-rats. 3. Thoracic aortae obtained from rats at 180 min after LPS showed a significant reduction in the contractile responses elicited by NA (10-9- 10-6 M). Pretreatment with aminoguanidine (15 mg kg- 1, i.v.,at 20 min prior to LPS) significantly prevented this LPS-induced hyporeactivity to NA ex vivo.4. Endotoxaemia for 180 min resulted in a significant increase in iNOS activity in the lung from 0.6 +/- 0.2 pmol mg-1 min-1 (control, n = 4) to 4.8 +/- 0.3 pmol mg-1 min-1 (P<0.05, n = 6). In LPS-rats treated with aminoguanidine, iNOS activity in the lung was attenuated by 44+/- 5% (n = 6, P <0.05).Moreover, when added in vitro to lung homogenates obtained from LPS-rats, aminoguanidine and N omega-nitro-L-arginine methyl ester (L-NAME; 10-8 to 10-3 M) caused a concentration-dependent inhibition of iNOS activity (n = 3-6, IC50: 30 +/- 12 and 11 +/- 6pEM, respectively P>0.05). In contrast,aminoguanidine was a less potent inhibitor than L-NAME of the constitutive nitric oxide synthase in rat brain homogenates (n = 3-6, IC50 is 140 +/- 10 and 0.6 +/- 0.1 I1M, respectively, P<0.05). In addition, the inhibitory effect of aminoguanidine on iNOS activity showed a slower onset than that of L-NAME(maximal inhibition at 90 min and 30 min, respectively).5. Treatment of conscious Swiss albino (T/O) mice with a high dose of endotoxin (60 mg kg-1, i.p.)resulted in a survival rate of only 8% at 24 h (n = 12). However, therapeutic application of aminoguanidine (15 mg kg-1, i.p. at 2 h and 6 h after LPS) increased the 24 h survival rate to 75%(n = 8), whereas L-NAME (3 mg kg-1, i.p. at 2 h and 6 h after LPS) did not affect the survival rate(11%, n=9).6 Thus, aminoguanidine inhibits iNOS activity and attenuates the delayed circulatory failure caused by endotoxic shock in the rat and improves survival in a murine model of endotoxaemia. Aminoguanidine,or novel, more potent selective inhibitors of iNOS may be useful in the therapy of septic shock.
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PMID:Aminoguanidine attenuates the delayed circulatory failure and improves survival in rodent models of endotoxic shock. 754 Dec 82

1. We have investigated whether glibenclamide, an inhibitor of ATP-sensitive potassium channels, influences the induction of the calcium-independent isoform of nitric oxide synthase (iNOS) in cultured J774.2 macrophages activated by bacterial endotoxin (E.coli lipopolysaccharide; LPS), as well as in the lung and aorta of rats with endotoxic shock. 2. Pretreatment of J774.2 macrophages with glibenclamide (10(-7) to 10(-5) M for 30 min) dose-dependently inhibited the accumulation of nitrite caused by LPS (1 microgram ml-1). In contrast, pretreatment of macrophages with tetraethylammonium (10(-4) to 10(-2) M for 30 min), a non-selective inhibitor of potassium channels, did not affect the rise in nitrite caused by LPS. At the highest concentration (10(-5) M) used, cromakalim, an opener of ATP-sensitive potassium channels, caused a small, but significant inhibition of nitrite formation in macrophages activated with LPS, while lower concentrations (10(-7) to 3 x 10(-6) M) were without effect. 3. The inhibition by glibenclamide (3 microM) of the increase in nitrite induced by LPS in J774.2 macrophages was weaker when glibenclamide was given several hours after LPS, indicating that glibenclamide inhibits the induction, but not the activity, of iNOS. In contrast, the degree of inhibition of nitrite formation caused by the nitric oxide synthase (NOS) inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) was similar when this agent was given up to 10 h after LPS. 4.In anaesthetized rats, LPS caused a fall in mean arterial blood pressure (MAP) from 120 +/-(time 0)to 98 +/- mmHg at 180 min (P<0.05, n = 6). Treatment of LPS-rats with glibenclamide (1 mg kg-1, i.v.at 60 min after LPS) caused a rapid and sustained rise in MAP (e.g. MAP at 180 min after LPS:122 +/-4 mmHg; n =6, P <0.05 when compared to LPS-rats). The maximum of the rise in MAP produced by glibenclamide (1 mg kg-1 , i.v.) was similar when the drug was given either at 60 or 180 min after LPS. However, the duration of the pressor response was significantly longer when glibenclamide was given at 60 min, rather than at 180 min after LPS.5. LPS-treatment caused a significant reduction of the pressor responses elicited by noradrenaline (NA,1 microg kg-1, i.v.) from 35 +/- 2 to 19 +/- 1 mmHg at 60 min and 20 +/- 2 mmHg at 180 min (P<0.05).Treatment of LPS-rats with glibenclamide (1 mg kg-1, i.v. at 60 min) caused a significant restoration of the pressor responses elicited by NA from 19 +/- 1 mmHg at 60 min (prior to glibenclamide injection) to 29 +/- 3 mmHg at 180 min (P<0.05).6. Endotoxaemia for 180 min resulted in a significant increase in a calcium-independent NOS activity(which was taken to represent iNOS activity) in the lung from 0.17 +/- 0.1 (control, n =4) to 6.21 +/- 0.48 pmol mg-1 min-1 (n =6, P<0.05). Injection of glibenclamide (1 mg kg-1, i.v.) at 60 min after LPS attenuated the increase in iNOS activity caused by endotoxaemia in the lung by 43 +/- 7%(n = 6, P <0.05). In contrast, injection of glibenclamide at 180 min after LPS did not result in a significant inhibition of iNOS activity (n = 6, P <0.05. 7. Thoracic aortae obtained from rats at 180 min after LPS showed a significant reduction in the contractions elicited by noradrenaline (NA, 10-9 to 10-6 M). Treatment of LPS-rats with glibenclamide(1 mg kg-1, i.v. at 60 min after LPS) significantly alleviated this LPS-induced hyporeactivity to NA ex vivo. In contrast, when aortic rings from LPS-rats were incubated in vitro with glibenclamide (10 microM for 20 min), glibenclamide did not reverse the vascular hyporeactivity to NA. However, L-NAME (300 microM for 20 min) significantly enhanced the contractile response to NA in aortic rings obtained from LPS-rats(P<0.05, n=6).8. No significant amounts of tumour necrosis factor-alpha (TNF alpha) were detectable in the plasma before the injection of LPS. Endotoxaemia for 90 min resulted in a significant rise in plasma TNFalpha levels(0.05 +/- 0.05 ng ml-1 at time 0, 3.78 +/- 0.24 ng ml-1 at 90 min, n = 6, P < 0.05). Treatment of LPS-rats with glibenclamide (1 mg kg-1, i.v. at 15 min prior to LPS, n = 5) did not significantly reduce the rise in plasma TNF alpha levels caused by endotoxin.9. Thus, glibenclamide inhibits the induction, but not the activity, of iNOS in vitro and in vivo. This inhibition of iNOS induction may contribute to the beneficial haemodynamic effects of glibenclamide in endotoxic shock.
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PMID:Glibenclamide-induced inhibition of the expression of inducible nitric oxide synthase in cultured macrophages and in the anaesthetized rat. 754 32

Diabetes is known to cause impaired endothelium-dependent relaxation of blood vessels. The purpose of this study was to determine whether this endothelial dysfunction is a permanent defect or is reversible after acute arginine supplementation in vitro or by surgical intervention in vivo using syngeneic pancreatic islet transplantation. Lewis rats were injected with streptozotocin to induce diabetes and were studied either 8 or 12 weeks later. Another group received syngeneic islets via intraportal injection at 8 weeks of diabetes and were allowed to become euglycemic for 4 weeks before study. Thoracic aortic rings were tethered in isolated muscle baths, contracted with a submaximal concentration of norepinephrine, and challenged with either the endothelium-dependent vasodilator acetylcholine or the endothelium-independent vasodilator nitroglycerin. Relaxation to acetylcholine (but not nitroglycerin) was reduced in both 8- and 12-week diabetic rings compared with age-matched control rings. Preincubation of diabetic rings in vitro with L-arginine (but not D-arginine) restored relaxation to acetylcholine to normal to rings from 8-week but not 12-week diabetic animals. Plasma basic amino acids (arginine, lysine, and histidine) were reduced by diabetes, whereas other neutral or acidic amino acids were unchanged (phenylalanine, proline, and glutamate), reduced (serine, cysteine, threonine, tyrosine, tryptophan, and aspartate), or elevated (isoleucine, leucine, and valine). Islet transplantation restored to normal the changes in plasma amino acids. Elevation in blood glucose and total glycosylated hemoglobin in diabetic animals was normalized after islet transplantation. Furthermore, islet transplantation completely restored the defective endothelium-dependent relaxation to acetylcholine in diabetic rings.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Syngeneic pancreatic islet transplantation reverses endothelial dysfunction in experimental diabetes. 765 36

Deendothelialized rings of rabbit aorta relax after exposure to UV light because of release of a relaxing factor that is similar if not identical to nitric oxide. We tested the hypothesis that production of the photo-induced relaxing factor is impaired in a rat model of genetic hypertension. Thoracic aortas were removed from adult Wistar-Kyoto rats and stroke-prone spontaneously hypertensive rats. The vessels were cut into rings, denuded of endothelium, and placed in a muscle bath for isometric force measurement. Rings were contracted with phenylephrine, and relaxation was measured after exposure to UV light. Aortic rings from stroke-prone spontaneously hypertensive rats relaxed to a greater extent after exposure to UV light than did rings from Wistar-Kyoto rats. An inhibitor of nitric oxide synthase (N omega-nitro-L-arginine) greatly potentiated the relaxation responses to light in both strains, and these enhanced relaxations were attenuated by tetraethylammonium chloride, potassium chloride, ouabain, or inhibitors of guanylate cyclase. These results suggest that UV irradiation induces relaxation in aortic smooth muscle that is greater in hypertensive than normotensive rats and is greatly enhanced after addition of inhibitors of nitric oxide production. Thus, the unidentified photo-induced relaxing factor is not solely nitric oxide but may also represent either a hyperpolarizing factor, because depolarization blocks the responses entirely, or possibly smooth muscle guanylate cyclase that might itself be photoactivable.
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PMID:A photoactivable source of relaxing factor in genetic hypertension. 820 24

We have shown that chronic administration of the nitric oxide (NO) precursor L-arginine inhibits atherogenesis in the hypercholesterolemic rabbit. However, the effect of supplemental arginine on preexisting lesions is not known and was the focus of the present study. New Zealand White rabbits received normal chow or 0.5% cholesterol chow for 10 weeks. Subsequently, L-arginine (2.25% in drinking water; ARG group) or vehicle (CHOL group) was administered for an additional 13 weeks, while the high-cholesterol diet was continued. Thoracic aortae were harvested at weeks 10, 14, 18, or 23. Rings of aorta were used to assess NO-dependent vasodilation to acetylcholine. Maximal relaxation to acetylcholine in the CHOL rabbits became progressively attenuated from 53.4% (at week 10) to 17.4% (by week 23). Planimetry of the luminal surface of the aortae from CHOL animals revealed a progressive increase in lesion surface area from 30.3% (at week 10) to 56.5% (by week 23). By contrast, animals in the ARG groups manifested improved endothelium-dependent relaxation associated with a reduction of lesion surface area at 14 and 18 weeks. The arginine-induced improvement in endothelium-dependent relaxation was associated with an increased generation of vascular NO and a reduced generation of vascular superoxide anion. By 23 weeks, 3 of 7 ARG animals had persistent improvement in NO-dependent vasodilation and exhibited a further reduction of lesion surface area tc 5.4%. We conclude that hypercholesterolemia induces a progressive loss of NO-dependent vasodilation associated with progressive intimal lesion formation. Administration of L-arginine to animals with preexisting intimal lesions augments vascular NO elaboration, reduces superoxide anion generation, and is associated with a reduction in lesion surface area. This is the first demonstration that restoration of NO activity can induce regression of preexisting intimal lesions and provides evidence that L-arginine therapy may be of potential clinical benefit.
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PMID:Regression or progression. Dependency on vascular nitric oxide. 854 25

We tested the hypothesis as to whether elevated arterial pressure in hypertension alters cGMP, or cAMP, mediated vasorelaxation. Relaxation to nitroglycerin and isoproterenol was determined in isolated aortic rings from one-kidney, one clip hypertensive (1K1C), coarctation hypertensive (CH) and normotensive control (C) rats. Thoracic aortas from 1K1C and CH rats, as well as abdominal aortas from 1K1C rats, but not abdominal aortas from CH rats were exposed chronically (4-6 weeks) to elevated arterial pressure. Sensitivity of rings with and without endothelium to nitroglycerin was suppressed significantly only in vessels exposed chronically to high arterial pressure. Impaired sensitivity to nitroglycerin in abdominal rings from 1K1C rats could not be abolished by exposure to 100 uM L-arginine, the substrate for production of NO by endothelial nitric oxide synthase, or 100 uM L-cysteine, the source of thiol groups required for the production of nitric oxide from nitroglycerin. Maximum relaxation to isoproterenol was impaired significantly in thoracic and abdominal rings, with and without endothelium, from 1K1C and CH rats. Relaxation to 8-bromo-cGMP and dibutyryl cAMP was similar in abdominal rings from all groups. We conclude that impaired vasorelaxation to nitroglycerin and isoproterenol in hypertension involves mechanisms prior to activation of vascular smooth muscle cGMP-dependent and cAMP-dependent protein kinase, respectively. Impaired cGMP, but not cAMP, mediated relaxation of aortas appears to result from their exposure to high arterial pressure per se. This effect does not appear to involve the vascular endothelium or vascular sources of thiols, but rather may reflect an effect of high arterial pressure to impair the ability of the artery to respond to nitric oxide derived from nitroglycerin.
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PMID:Selective effect of high arterial pressure in hypertension upon inhibition of cGMP versus cAMP mediated vascular relaxation. 884 63

This study tested the hypothesis that exogenous nitric oxide (NO) inhibits basal release of NO in isolated rat aortic rings and in vivo. Thoracic aortic rings were suspended in organ chambers with Krebs-Henseleit solution. In untreated rings, the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) markedly increased basal vascular tone by 34.6 +/- 5.2% of maximal force produced by 100 nM thromboxane A2 mimetic U-46619, indicating a basal release of NO. Other rings were pretreated with the exogenous NO donor S-nitroso-N-acetylpenicillamine (SNAP) for 20 min and then washed free of drug. In these rings, L-NAME-induced vasoconstriction was significantly attenuated in a concentration-dependent manner (from 34.6 +/- 5.2 to 25.7 +/- 2.9% at SNAP = 0.5 microM, 15.2 +/- 3.1% at 1 microM, and 11.9 +/- 2.5% at 5 microM), while having no effect on NO-independent phenylephrine-induced vasoconstriction (35.4 +/- 4.7 untreated vs. 41.3 +/- 4.3% SNAP pretreated, not significant). In addition, the nonnitrosylated parent molecule of SNAP, acetylpenicillamine, had no effect on the vasoconstriction induced by L-NAME. In the in vivo studies in anesthetized rats, L-NAME caused significant hypertensive responses (34 +/- 4-mmHg increase in mean arterial blood pressure). Subvasoactive doses of SNAP attenuated these hypertensive responses in a dose-dependent manner (20 +/- 3-mmHg increase with 10 micrograms/kg SNAP pretreatment and 16 +/- 4-mmHg increase with 20 micrograms/kg SNAP pretreatment), but any dose of acetylpenicillamine studied had no effect. Coadministration of superoxide dismutase and SNAP significantly potentiated the inhibitory effect of the NO donor on vasocontraction responses to L-NAME. Furthermore, SNAP did not attenuate the hypertensive responses to phenylephrine. These results indicate that exogenous NO significantly inhibits basal NO release both in vitro and in vivo, suggesting that NO plays an important negative-feedback regulatory role under physiological conditions.
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PMID:Exogenous NO inhibits basal NO release from vascular endothelium in vitro and in vivo. 894 24

We report the case of a patient who was admitted in hospital for evaluation of a superior vena cava thrombosis. The patient exhibited an activated protein C resistance due to an arginine-506 mutation in factor V. Thoracic CT-scan showed a non-compressive complete superior vena cava thrombosis. Other investigations revealed a pleural effusion associated with an ovarian tumor. Pathological data of pleural biopsies showed a papillar carcinoma. Ovarian neoplasia revealed by a paraneoplasic syndrome was diagnosed. Treatment associated cyclophosphamide and carboplatin with anti-K-vitamin was administrated, with a complete remission and disappearance of superior vena cava thrombosis at 27 months of evolution. At this date, we observed a local pelvis recurrence which was treated with paclitaxel associated with surgery.
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PMID:[Paraneoplastic superior vena cava thrombosis disclosing an ovarian tumor]. 903 6


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